P1483: LONG-TERM IMPACT OF OLIPUDASE ALFA ENZYME REPLACEMENT THERAPY ON SPLEEN VOLUME AND HEMATOLOGIC MANIFESTATIONS IN CHILDREN AND ADULTS WITH CHRONIC ACID SPHINGOMYELINASE DEFICIENCY
Authors: Jesus Villarrubia, Jaya Ganesh, Roberto Giugliani, Nathalie Guffon, Eugen Mengel, Maurizio Scarpa, Melissa Wasserstein, Nicole Armstrong, Gasparic Maja, Yong Kim, Holly Wong, Abhimanyu Yarramaneni
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease types A and B, is an underrecognized and debilitating lysosomal storage disease. Deficient ASM activity results in progressive visceral, hematologic, and pulmonary dysfunction across a disease spectrum, with CNS manifestations in the most severe patients. Splenomegaly (often exceeding 15 multiples of normal [MN]), thrombocytopenia, and anemia are common in ASMD and lead to increased risk of bleeding and splenic rupture. Hematologic abnormalities may prompt undiagnosed ASMD patients to seek medical care; thus, disease awareness among hematologists may help reduce diagnostic delays. Enzyme replacement therapy with olipudase alfa (recombinant human ASM), the first disease-modifying treatment for ASMD, was recently approved in the EU, the US, and >30 other countries for treatment of non-CNS manifestations of ASMD in children and adults. Aims: To assess the impact of 2 years of olipudase alfa treatment on spleen volume and hematologic outcomes in adults and children with ASMD. Methods: We evaluated data from the 34 adults in the ASCEND trial and extension (NCT02004691, Sanofi) who had baseline and 2-year values on olipudase alfa (excluding data during placebo treatment) and the 20 children from the ASCEND-Peds open-label trial and extension (NCT02292654/NCT02004704, Sanofi) who had baseline and 2-year treatment values. We report the mean percent change ± SD in spleen volume (in MN), platelet count, and hemoglobin from baseline to 2 years. Results: At baseline, all patients had splenomegaly, 90% of adults and 70% of children had platelet counts <150 x 109/L, and 29% of adults and 18% of children were anemic (WHO classification based on age and sex). After 2 years on olipudase alfa, all patients had a decrease in spleen volume. Spleen volume decreased in adults by a mean of 47.2% ± 8.3% (from 11.4 ± 5.0 to 5.9 ± 2.6 MN, n=22) and in children by 60.9% ± 8.7% (from 19.1 ± 9.0 to 7.2 ± 3.3 MN, n=19). Platelet count increased after 2 years of treatment in adults by a mean of 17.2 ± 23.3% (from 110 ± 29 to 127 ± 34 x 109/L, n=22) and in children by 28.7% ± 28.3% (from 131 ± 48 to 167 ± 65 x 109/L, n=14). Hemoglobin increased after 2 years of treatment in adults by a mean of 3.3 ± 7.3% (from 134 ± 17 to 138 ± 15 g/L, n=22) and in children by 3.3 ± 7.5% (from 125 ± 16 to 129 ± 13 g/L, n=14). No patient developed new thrombocytopenia or new anemia after 2 years of olipudase alfa. Improvement was also seen in pulmonary function tests, liver volume, liver function tests, and dyslipidemia. Olipudase alfa was generally well tolerated in both adults and children with no trial discontinuations due to treatment-related adverse events, although COVID-19 restrictions resulted in some missed assessments. Summary/Conclusion: After 2 years of olipudase alfa treatment, mean spleen volume decreased by 47% in adults and 61% in children, and mean platelet count increased by 17% in adults and 29% in children. Mean hemoglobin levels, which were mostly normal at baseline, increased slightly in adults and children. No adult or child had an increase in spleen volume or new thrombocytopenia or anemia after 2 years of treatment. These findings suggest that olipudase alfa improves 2-year spleen volume and hematologic outcomes in patients with ASMD. Keywords: Platelet count, Enzyme replacement therapy, Lysosomal storage disease, Genetic